A Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 in Major Depressive Disorder (X-NOVA)

A Proof-of-Concept, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 in Major Depressive Disorder

This is a multicenter, Phase 2, double-blind, randomized, parallel-arm, placebo-controlled clinical trial to evaluate the efficacy, safety, and tolerability of XEN1101 in subjects with Major Depressive Disorder.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: XEN1101 10 mg; Drug: XEN1101 20 mg

Detailed Description

The study is divided into 3 stages: Screening - up to 4 weeks duration; Treatment - 6 weeks duration; Follow-up - 4 weeks duration. The total study duration per subject is estimated to be approximately 14 weeks.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Medical Affairs; Phone Number: 1-604-484-3300; Email: XenonCares@xenon-pharma.com

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center
    • Lafayette, California, United States, 94549
      • Sunwise Clinical Research, LLC
    • Pico Rivera, California, United States, 90660
      • California Neuropsychopharmacology Clinical Research Institute
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
  • Florida
    • Miami, Florida, United States, 33014
      • Meridian International Research
    • Miami, Florida, United States, 33125
      • Global Medical Institutes (GMI)
    • Miami, Florida, United States, 33133
      • CCM Clinical Reseach Group, LLC
  • Georgia
    • Decatur, Georgia, United States, 30030
      • i-Research, Atlanta
    • Marietta, Georgia, United States, 30060
      • Psych Atlanta, PC
    • Savannah, Georgia, United States, 31405
      • IResearch
  • Illinois
    • Elgin, Illinois, United States, 60123
      • Revive Research Institute, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research
  • New Jersey
    • Marlton, New Jersey, United States, 08009
      • Hassman Research Institute
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc. (NBR)
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine, PLLC
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Richard M Weisler and Association
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Plano, Texas, United States, 75093
      • AIM Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Be properly informed of the nature and risks of the study and given written informed consent.
• Male or female, aged 18 through 65 years (inclusive) with a body mass index (BMI) ≤35 kg/m².
• Subject must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for current MDD and currently in a moderate to severe major depressive episode (MDE), confirmed using the Mini International Neuropsychiatric Interview (MINI).
• Current MDE duration ≥2 months and <24 months at the time of screening.
• Current illness severity that is at least moderate, defined as a score of ≥20 on the HAM-D17 at screening and on Day 1.
• Score ≥20 on the SHAPS at screening and on Day1.
• Must be willing to comply with the study protocol for the full term of the study.

Key Exclusion Criteria:

• A primary psychiatric diagnosis other than MDD as defined by DSM-5 (comorbid anxiety disorders [including agoraphobia, generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), and panic disorder] are allowed).
• Concomitant use of antidepressants and/or other disallowed pharmacotherapy (including benzodiazepines).
• History of schizophrenia or other psychotic disorder, MDD with psychotic features, bipolar I or II disorder, or MDD with mixed features.
• History of non-response to >1 antidepressant drug due to lack of efficacy in the current MDE.
• Failing >3 antidepressant drug trials, for any reason, in the current MDE.
• History of non-response to electroconvulsive therapy (ECT) in the past 10 years.
• Active suicidal plan/intent in the past 6 months, or more than 1 lifetime suicide attempt.
• Females who are pregnant, breastfeeding, or planning to become pregnant during the first administration of study drug until 3 months after the last dose of study drug.
• Meets criteria for a substance use disorder within the past 12 months, with the exception of tobacco use, and/or has a positive urine toxicology screen for drugs of abuse.
• Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XEN1101 10 mg; During the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 10 mg, orally with food, per day	Drug: XEN1101 10 mg; XEN1101 oral capsule
Experimental: XEN1101 20 mg; During the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 20 mg, orally with food, per day	Drug: XEN1101 20 mg; XEN1101 oral capsule
Placebo Comparator: placebo; During the double blind treatment period (42 days), subjects will take 1 capsule of placebo, orally with food, per day	Drug: Placebo; Placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score.	From baseline to end of treatment (Week 6).
Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuations.	From randomization to Week 10.

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Snaith-Hamilton Pleasure Scale (SHAPS) score.	From baseline to end of treatment (Week 6).
Change in Beck Anxiety Inventory (BAI) score.	From baseline to end of treatment (Week 6).

Collaborators and Investigators

• Sponsor: Xenon Pharmaceuticals Inc.
• Investigators: Study Director: Study Director, Xenon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2022
• Primary Completion (Actual): September 18, 2023
• Study Completion (Actual): October 16, 2023

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Depression; Major Depressive Disorder; Potassium channel
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: XPF-008-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No